Abstract P3-09-04: Phase 2, open-label study of intratumoral tavokinogene telseplasmid (tavo) plus electroporation in combination with intravenous pembrolizumab therapy in patients with inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC) (KEYNOTE- 890/OMS-I141)

摘要: BACKGROUND: Anti-PD-1 checkpoint inhibitor (CPI) monotherapy has demonstrated modest activity in pre-treated mTNBC, with single digit objective response rates (ORR) observed. Our prior data suggests that local electroporation after intratumoral administration of tavokinogene telseplasmid (IT-tavo-EP), a plasmid encoding the proinflammatory cytokine IL-12, can render CPI non-responsive mTNBC sensitive to therapy. The phase II KEYNOTE-890/OMS-I141 study was therefore designed evaluate IT-tavo-EP and IV pembrolizumab patients previously treated chemotherapy +/- METHODS: Patients histologically confirmed inoperable locally advanced or metastatic TNBC at least 1 line systemic therapy for disease, including therapy, were eligible. required have RECIST v1.1 measurable disease anatomically distinct cutaneous subcutaneous lesion accessible injection electroporation. Scans obtained every 12 weeks. received 200 mg on day each 3-week cycle concentration 0.5 mg/mL dose volume ~1/4 calculated lesion(s) days 1, 5, 8 6 primary endpoint this open-label, non-randomized trial is ORR by investigator review. Secondary endpoints include safety tolerability combined duration response, progression-free survival (PFS), immune PFS overall survival. correlation between changes cell subsets treatment also evaluated. RESULTS: At time abstract submission, 16 planned 25 been enrolled 11 completed post-treatment assessment initial 12-week evaluation discontinued assessment. had median 3 lines disease. Partial responses observed (ORR 27.3%), deep patient multiple liver, bone, skin nodal metastases short disease-free interval following neoadjuvant chemotherapy. Regression untreated lesions Treatment well tolerated any grade emergent adverse events (AEs) regardless attribution (68.8%) [grade ≥3 (37.5%)]. Only one AE attributed none IT-tavo EP. immunological blood consistent an IL-12-associated mechanism action, on-treatment reduction peripheral gMDSC suppressors. Additional biomarker analysis tumor samples are ongoing. CONCLUSIONS: When compared results KEYNOTE-086, which 5.3% pretreated monotherapy, our preliminary from who reached time-point may enhance sensitivity population. Updated will be presented. Citation Format: Melinda L. Telli, Irene Wapnir, Bianca Devitt, Katharine Cuff, Hatem Soliman, Shaveta Vinayak, David A. Canton, Christopher Twitty, Kellie Malloy Foerter, Rohit Joshi. Phase 2, open-label (tavo) plus combination intravenous triple-negative breast cancer (mTNBC) (KEYNOTE- 890/OMS-I141) [abstract]. In: Proceedings 2019 San Antonio Breast Cancer Symposium; Dec 10-14; Antonio, TX. Philadelphia (PA): AACR; Res 2020;80(4 Suppl):Abstract nr P3-09-04.